The use of magnetic fields to separate magnetic material from non-magnetic material in, e.g., fluid-like media or suspensions has been recognized as a technique potentially useful in biological and biochemical separation processes. U.S. Pat. Nos. 3,700,555, and 3,970,518, e.g., disclose magnetic separation models for separating lymphocytes from blood samples, and in clinical immunoassays. The disclosures show that magnetic material may be treated so that substances, such as antigens, will attach or bind to the surface of magnetic material. Once attached or bound, these substances may be separated out of a medium when a magnetic field is applied thereto, because the magnetic field will, naturally, draw the magnetic material out of the medium. The attached substance will separate out of the medium together with the magnetic material, and may then be separated therefrom by treatment with separating agents.
One problem with the presently available methods of magnetic separation is that the particle forms of magnetic material which have been in use must be coated, or treated extensively to provide a binding or attaching site for molecular attachment. Magnetic material, unless treated, does not provide sufficient, stable attachment or binding sites for biological or biochemical material. As a result, magnetic separation techniques have been hampered either by the need for extensive pretreatment of the magnetic material, or have yielded poor results when there has been no pretreatment.
Recently, magnetotactic bacteria have been discovered in nature, and have been found to be amenable to cultivation in the laboratory. See, e.g., Frankel, Blakemore & Wolfe, Science, v. 203, pp. 1355-56 (1979); Maugh, Science, v. 215, pp. 1492-1493; Blakemore, Maratea & Wolfe, Journal of Bacteriology, v. 140, No. 2, pp. 720-29 (November 1979); Blakemore, Science, v. 190, pp. 377-79 (1975). In addition, the following U.S. patents, the disclosures of which are incorporated by reference herein, disclose aspects of magnetic or magnetotactic bacteria and their cultivation. U.S. Pat. No. 4,385,119, discloses pure cultures of a strain of magnetotactic Aquaspirillum, designated as strain MS-1 and American Type Culture Collection identification number ATCC 31632, and U.S. Pat. No. 4,394,451, discloses methods and media for culturing a magnetotactic bacteria, including strain MS-1. These magnetotactic bacteria are magnetotactic because of the presence of particles of magnetite, Fe.sub.3 O.sub.4, enclosed within sheaths or membranes in the bacteria. These sheath-enclosed particles of magnetite, or magnetosomes as they are called, exist as independent particles, or in arrays or chains. The magnetosomes are, naturally, magnetic even when removed from the bacteria. The bacteria and magnetosomes possess qualities which are highly useful for use in magnetic separation methods. For example, the bacteria and magnetosomes are highly uniform in size, shape, and magnetic properties, so behavior of a sample of either magnetotactic bacteria or magnetosomes in a magnetic field gradient will be uniform, with little allowance necessary for variations in physical properties. The bacteria and magnetosomes possess high dipole moments, so these will migrate easily to a stronger magnetic field gradient. Additionally intracellular or intramembranous magnetite increases the density of the bacteria or magnetosomes, which, in terms makes both of these suitable for use in separation by centrifugation.
Hence it is an object of this invention to provide a magnetic separation method in which magnetic bacteria are used.
It is a further object of the invention to provide a method of magnetic separation wherein magnetosomes or the magnetic material therein are used.
It is a still further object of the invention to provide a method of quantitative analysis, using magnetic bacteria or magnetosomes.
How these and other objects of the invention are accomplished will become apparent in light of the accompanying disclosure.